Cross species analyses are among the most powerful methods for deeply annotating model genomes. A draft sequence of D. pseudoohscura will be generated by a whole genome shotgun method using a mixture of 2.0 and 10-kb plasmids, and fosmid and BAC ends. The data will be assembled using modules of the Atlas assembler developed at the Baylor College of Medicine Human Genome Sequencing Center. The initial assembly will yield contigs of average length 14-kb with about one half of the approximately 15,000 genes represented on single contigs with at least 2.0-kb of contiguous upstream sequence. Alignment of these with the existing D. melanogaster sequence will display the 5? cis-regulatory elements. Directed sequence top-off efforts and a modest amount of EST and cDNA sequencing will then ensure that the remainder of all D. pseudoobscura genes are fully represented. Two innovations for computer analysis of large sequence data sets will be explored. The per read cost for this work will be less than $1.80.